Discovery and design of carbohydrate-based therapeutics

Expert Opinion on Drug Discovery

Volumn 5, Issue 8, 2010, Pages 721-737

  Cipolla, Laura ^a   Arajo, Ana C ^b   Bini, Davide ^a   Gabrielli, Luca ^a   Russo, Laura ^a   Shaikh, Nasrin ^a  

^a UNIVERSITY OF MILANO BICOCCA   (Italy)

^b UNIVERSITY OF LISBON   (Portugal)

Author keywords

Antibacterials; Anticancer agents; Carbohydrate chemistry; Carbohydrate based therapeutics; Glycochemistry; Glycomedicine; Vaccines

Indexed keywords

1 DEOXYNOJIRIMYCIN; ACARBOSE; CANCER VACCINE; CARBOHYDRATE; DIPHTHERIA TOXOID CRM197; FONDAPARINUX; GLYCAN; GLYCOPROTEIN; HEPARAN SULFATE; HEPARIN; IDRAPARINUX; LIPOPOLYSACCHARIDE; MIGLITOL; MIGLUSTAT; NOJIRIMYCIN; OSELTAMIVIR; PNEUMOCOCCUS VACCINE; POLYSACCHARIDE VACCINE; QUIMI HIB; SOMATOSTATIN; SWAINSONINE; TETRAHYDROFURAN; THERATOPE; TRIPALMITOYL PALMITOYL S GLYCERYLCYSTEINYLSERINE; TUMOR ASSOCIATED CARBOHYDRATE ANTIGEN; UNCLASSIFIED DRUG; VALIDAMYCIN A; ZANAMIVIR;

CELL ADHESION; CLINICAL TRIAL; CONTROLLED STUDY; DEEP VEIN THROMBOSIS; DIPHTHERIA; EXTRACELLULAR MATRIX; GAUCHER DISEASE; HUMAN; IMMUNE RESPONSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PNEUMOCOCCAL INFECTION; PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN GLYCOSYLATION; PROTEIN STRUCTURE; REVIEW;

ANIMALS; BACTERIAL VACCINES; CARBOHYDRATE CONFORMATION; CARBOHYDRATES; DRUG DESIGN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77954764523     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.2010.497811     Document Type: Review

References (155)

1. Gabius H-J. The sugar code: fundamentals of glycoscience. Wiley-Blackwell; 2009
2. Varki A. Nothing in glycobiology makes sense, except in the light of evolution. Cell 2006;126:841-845
3. Bishop JR, Gagneux P. Evolution of carbohydrate antigens - microbial forces shaping host glycomes. Glycobiology 2007;17:23R-34R
4. Messner P, Schaffer C. Prokaryotic glycoproteins. Prog Chem Org Nat Prod 2003;85:51-124
5. Werz DB, Ranzinger R, Herget S, et al. Exploring the structural diversity of mammalian carbohydrates ("Glycospace") by statistical databank analysis. ACS Chem Biol 2007;2:685-691
6. Ritchie GE, Moffatt BE, Morgan BP, et al. Glycosylation and the complement system. Chem Rev 2002;102:305-319
7. Dove A. The bittersweet promise of glycobiology. Nat Biotechnol 2001;19:913-917
8. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell 2006;126:855-867
9. Lowe JB, Marth JD. A genetic approach to mammalian glycan function. Annu Rev Biochem 2003;72:673-691
10. Freeze HH. Genetic defects in the human glycome. Nat Rev Genet 2006;7:537-551
11. Dwek RA, Butters TD, Platt FM, Zitzmann N. Targeting glycosylation as a therapeutic approach. Nat Rev Drug Discov 2002;1:65-75
12. Van Kooyk Y, Rabinovich GA. Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol 2008;9:593
13. Hakomori S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA 2002;99:10231-10233
14. Nangia-Makker P, Conklin J, Hogan V, Raz A. Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. Trends Mol Med 2002;8:187-192
15. Dube DH, Bertozzi CR. Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nat Rev Drug Discov 2005;4:477-488
16. Cobb BA, Kasper DL. Coming of age: carbohydrates and immunity. Eur J Immunol 2005;35:352-356
17. Brandenburg K, Andra J, Muller M, et al. Physicochemical properties of bacterial glycopolymers in relation to bioactivity. Carbohydr Res 2003;338:2477-2489
18. Ohto U, Fukase K, Miyake K, Satow Y. Crystal structures of human MD-2 and its complex with antiendotoxic lipid iva. Science 2007;316:1631-1634
19. Zimmer SM, Zughaier SM, Tzeng Y, Stephens DS. Human MD-2 discrimination of meningococcal lipid a structures and activation of TLR4. Glycobiology 2007;17:847-856
20. Brandenburg K, Wiese A. Endotoxins: relationships between structure, function, and activity. Curr Top Med Chem 2004;4:1127-1146
21. Smith AE, Helenius A. How viruses enter animal cells. Science 2004;304:237-242
22. Raman R, Raguram S, Venkataraman G, et al. Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods 2005;2:817-824
23. Feizi T, Fazio F, Chai W, Wong C. Carbohydrate microarrays - a new set of technologies at the frontiers of glycomics. Curr Opin Struct Biol 2003;13:637-645
24. Feizi T. Progress in deciphering the information content of the glycome a crescendo in the closing years of the millennium. Glycoconj J 2000;17:553-565
25. Fukui S, Feizi T, Galustian C, et al. Oligosaccharide microarrays for high-throughput detection and specificity assignments of carbohydrate-protein interactions. Nat Biotechnol 2002;20:1011-1017
26. Fazio F, Bryan MC, Blixt O, et al. Synthesis of sugar arrays in microtiter plate. J Am Chem Soc 2002;124:14397-14402
27. Park S, Shin I. Fabrication of carbohydrate chips for studying protein-carbohydrate interactions. Angew Chem Int Ed Engl 2002;41:3180-3182
28. Paulson JC, Blixt O, Collins BE. Sweet spots in functional glycomics. Nat Chem Biol 2006;2:238-248
29. Harvey DJ. Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: an update for 2003-2004. Mass Spectrom Rev 2009;28:273-361
30. Kogelberg H, Solisy D, Jimenez-Barbero J. New structural insights into carbohydrate - protein interactions from NMR spectroscopy. Curr Opin Struct Biol 2003;13:646-653
31. Spiro RG. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 2002;12:43R-56R
32. Wong CH. Carbohydrate-based drug discovery. Wiley-VCH Weinheim; 2003
33. Landsteiner K. Individual differences in human blood. Science 1931;73:405-411
34. Morgan WTJ. Some immunological aspects of the products of the human blood group genes. Ciba Foundation Symposium, London; 1959
35. Watkins WM. Biochemistry and genetics of the ABO, Lewis and P blood group systems. Advances in human genetics: Plenum Publishing Corp., New York; 1980
36. Kabat EA. Contributions of quantitative Immunochemistry to knowledge of blood group a, B, H, Le, I and i antigens. Clin Pathol 1982;78:28l-92
37. Feizi T, Lloyd KO. An appreciation of Elvin A. Kabat (1914-2000): scientist, educator and a founder of modern carbohydrate biology. Glycoconj J 2000;17:439-442
38. Linhardt RJ. Heparin: an important drug enters its seventh decade. Chem Ind 1991;2:45-50
39. Shriver Z, Raguram S, Sasisekharan R. Glycomics: a pathway to a class if new and improved therapeutics. Nat Rev Drug Discov 2004;3:863-873
40. Seeberger PH. Automated carbohydrate synthesis as platform to address fundamental aspects of glycobiology-current status and future challenges. Carbohydr Res 2008;343:1889-1896
41. Boltje TJ, Buskas TG, Boons G. Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research. Nat Chem 2009;1:611-622
42. Seeberger PH. Automated oligosaccharide synthesis. Chem Soc Rev 2008;37:19-28
43. Davies BG. Recent developments in oligosaccharide synthesis. J Chem Soc Perkin Trans 2000;14:2137-2160
44. Werz DB, Seeberger PH. Carbohydrates as the next frontier in pharmaceutical research. Chem Eur J 2005;11:3194-3206
45. Arya P, Bugga VN, Sarma BS. Combinatorial carbohydrate chemistry. Organic Chemistry of Sugars. Taylor and Francis, CRC Press; 2006. pp. 729-754
46. Nicolau KC, Mitchell HG. Adventures in carbohydrate chemistry: new synthetic technologies, chemical synthesis, molecular design, and chemical biology. Angew Chem Int Ed 2001;40:1576-1624
47. Wang C, Lee J-C, Luo S-Y, et al. Regioselective one-pot protection of carbohydrates. Nature 2007;446:896-899
48. Zhu XM, Schmidt RR. New principles for glycoside-bond formation. Angew Chem Int Ed 2009;48:1900-1934
49. Pornsuriyasak P, Ranade SC, Li A, et al. STICS: surface-tethered iterative carbohydrate synthesis. Chem Commun 2009:1834-1836
50. Trincone A, Giordano A. Glycosyl hydrolases and glycosyltransferases in the synthesis of oligosaccharides. Curr Org Chem 2006;10:1163-1193
51. Hancock SM, Vaughan MD, Withers SG. Engineering of glycosidases and glycosyltransferases. Curr Opin Chem Biol 2006;10:509-519
52. Lairson LL, Henrissat B, Davies GJ, Wither SG. Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem 2008;77:521-555
53. Miller JS, Dudkin VJ, Lyon GJ, et al. Toward fully synthetic N-linked glycoproteins. Angew Chem Int Ed 2003;42:431-434
54. Yuan Y, Chen J, Wan Q, et al. Toward homogeneous erythropoietin: fine tuning of the C terminal acyl donor in the chemical synthesis of the Cys(29)-Gly(77) glycopeptide domain. J Am Chem Soc 2009;13:5432-5437
55. Naruchi K, Hamamoto T, Kurogochi M, et al. Construction and structural characterization of versatile lactosaminoglycan-related compound library for the synthesis of complex glycopeptides and glycosphingolipids. J Org Chem 2006;71:9609-9621
56. Wang Z, Zhou L, El-Boubbou K, et al. Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo H based on preactivation of thioglycosyl donors. J Org Chem 2007;72:6409-6420
57. Kim HM, Kim IJ, Danishefsky SJ. Total syntheses of tumor-related antigens: probing the feasibility limits of the glycal assembly method. J Am Chem Soc 2001;123:35-48
58. Ruttens B, Saksena R, Kovác P. Synthesis of phosphorylated, conjugation-ready Di-, Tri- and Tetrasaccharide Fragments of the O-Specific Polysaccharide of V. cholerae O139. Eur J Org Chem 2007:4366-4375
59. Holemann A, Seeberger PH. Carbohydrate diversity: synthesis of glycoconjugates and complex carbohydrates. Curr Opin Biotechnol 2004;15:615-622
60. De Meo C, Demchenko AV, Boons G. A stereoselective approach for the synthesis of r-Sialosides. J Org Chem 2001;66:5490-5497
61. Xia J, Aldefer JL, Piskorz CF, Matta KL. Total synthesis of sulfated and sialylated oligosaccharide chains from respiratory mucins. Chem Eur J 2000;6:3442-3451
62. Stallforth P, Lepenies B, Adibekian A, Seeberger PH. Carbohydrates: a frontier in medicinal chemistry. J Med Chem 2009;52:5561-5577
63. Petitou M, van Boeckel CA. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew Chem Int Ed 2004;43:3118-3133
64. Astronomo RD, Burton DR. Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov 2010;9:308-324
65. Guo H, Yi W, Song JK, Wang PG. Current understanding on biosynthesis of microbial polysaccharides. Curr Top Med Chem 2008;8:141-151
66. Bos MP, Robert V, Tommassen J. Biogenesis of the gram-negative bacterial outer membrane. Annu Rev Microbiol 2007;61:191-214
67. Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu Rev Immunol 1995;13:655-692
68. McCool TL, Harding CV, Greenspan NS, Schreiber JR. B- and T-cell immune responses to pneumococcal conjugate vaccines: divergence between carrier- and polysaccharide-specific immunogenicity. Infect Immun 1999;67:4862-4869
69. Vliegenthart JF. Carbohydrate based vaccines. FEBS Lett 2006;580:2945-2950
70. Pozsgay V. Recent developments in synthetic oligosaccharide-based bacterial vaccines. Curr Top Med Chem 2008;8:126-140
71. Nyame AK, Kawar ZS, Cummings RD. Antigenic glycans in parasitic infections: implications for vaccines and diagnostics. Arch Biochem Biophys 2004;426:182-200
72. Francis T Jr, Tillett WS. Cutaneous reactions in pneumonia. The development of antibodies following the intradermal injection of type-specific polysaccharide. J Exp Med 1930;52:573-585
73. Heidelberger M, Dilapi MM, Siegel M, Walter AW. Persistence of antibodies in human subjects injected with pneumococcal polysaccharides. J Immunol 1950;65:535-541
74. Jensen PE. Recent advances in antigen processing and presentation. Nat Immunol 2007;8:1041-1048
75. Carrico IS. Chemoselective modification of proteins: hitting the target. Chem Soc Rev 2008;37:1423-1431
76. Sletten EM, Bertozzi CR. Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed 2009;8:6974-6998
77. Gamblin DP, Scanlan EM, Davis BG. Glycoprotein synthesis: an update. Chem Rev 2009;109:131-163
78. Nicotra F, Cipolla L, Peri F, et al. Chemoselective neoglycosylation. Advances carbohydrate chemistry and biochemistry: Elsevier Science Direct; 2007
79. Lin YA, Chalker JM, Davis BG. Olefin metathesis for site-selective protein modification. ChemBioChem 2009;10:959-969
80. Verez-Bencomo V, Fernandez-Santana V, Hardy E, et al. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science 2004;305:522-525
81. Fernandez-Santana V, Cardoso F, Rodriguez A, et al. Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b. Infect Immun 2004;72:7115-7123
82. Seeberger PH, Werz DB. Synthesis and medical applications of oligosaccharides. Nature 2007;446:1046-1051
83. Wang LX. Toward oligosaccharide- and glycopeptide-based HIV vaccines. Curr Opin Drug Discov Devel 2006;9:194-206
84. Taylora RK, Kirna TJ, Bosea N, et al. Progress towards development of a cholera subunit vaccine chem. Biodiversity 2004;1:1036-1057
85. Barocchi MA, Censini S, Rappuoli R. Vaccines in the era of genomics: the pneumococcal challenge. Vaccine 2007;25:2963-2973
86. Hakomori SI. New direction in cancer therapy based on aberrant expression of glycosphingolipids. Cancer Cells 1991;3:461-470
87. Galonic DP, Gin DY. Chemical glycosylation in the synthesis of glycoconjugate antitumour vaccines. Nature 2007;446:1000-1007
88. Slovin SF, Keding SJ, Ragupathi G. Carbohydrate vaccines as immunotherapy for cancer. Immunol Cell Biol 2005;83:418-428
89. Cipolla L, Peri F, Airoldi C. Glycoconjugates in cancer therapy. Anticancer Agents Med Chem 2008;8:92-121
90. Danishefsky SJ, Allen JR. From the laboratory to the clinic: a retrospective on fully synthetic carbohydrate-based anticancer vaccines. Angew Chem Int Ed 2000;39:836-863
91. Holmberg LA, Sandmaier BM. Vaccination with theratope (STn-KLH) as treatment for breast cancer. Expert Rev Vaccines 2004;3:655-663
92. Lo-Man R, Vichier-Guerre S, Perraut R. A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn carbohydrate antigen induces tumor-specific antibodies in nonhuman primates. Cancer Res 2004;64:4987-4994
93. Buskas T, Thompson P, Boons GJ. Immunotheraphy for cancer: synthetic carbohydrate-based vaccines. Chem Commun 2009:5335-5349
94. Aliprantis AO, Yang RB, Mark MR, et al. Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 1999;285:736-739
95. Allen JR, Harris CR, Danishefsky SJ. Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewisy antigens. J Am Chem Soc 2001;123:1890-1897
96. Huang CY, Thayer DA, Chang AY, et al. Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. Proc Natl Acad Sci USA 2006;103:15-20
97. Ingale S, Wolfert MA, Gaekwad J. Robust immune responses elicited by a fully synthetic three component vaccine. Nat Chem Biol 2007;3:663-667
98. OReilly M, Paulson JC. Siglecs as targets for therapy in immune cell mediated disease. Trends Pharmacol Sci 2009;30:240-248
99. Crocker PR, Paulson JC, Varki A. Siglecs and their roles in the immune system. Nat Rev Immunol 2007;7:255-266
100. Kiessling LL, Gestwicki JE, Strong LE. Synthetic multivalent ligands as probes of signal transduction. Angew Chem Int Ed 2006;45:2348-2368
101. Brewer CF, Miceli MC, Baum LG. Clusters, bundles, arrays and lattices: novel mechanisms for lectin saccharide mediated cellular interactions. Curr Opin Struct Biol 2002;12:616-623
102. Mammen M, Choi SK, Whitesides GM. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew Chem Int Ed 1998;37:2755-2794
103. Kitov PI, Sadowska JM, Mulvey G, et al. Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands. Nature 2002;403:669-672
104. de Paz JL, Noti C, Bohm F, et al. Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers. Chem Biol 2007;14:879-887
105. Ernst B, Magnani JL. From carbohydrate leads to glycomimetic drugs. Nat Rev Drug Discov 2009;8:661-677
106. Koeller KM, Wong CH. Emerging themes in medicinal glycoscience. Nat Biotechnol 2000;18:835-841
107. Lillelund VH, Jensen HH, Liang X, Bols M. Recent developments of transition-state analogue glycosidase inhibitors of non-natural product origin. Chem Rev 2002;102:515-533
108. Murphy PV. Peptidomimetics, glycomimetics and scaffolds from carbohydrate building blocks. Eur J Org Chem 2007:4177-4187
109. Gravier-Pelletier C, Le Merrer Y. Synthesis of scaffolds with glycomimetic structures. Curr Org Synth 2007;4:1-13
110. Arjona O, Gomez AM, Lopez C, Plumet J. Synthesis and conformational and biological aspects of carbasugars. Chem Rev 2007;107:1919-2036
111. Compain P, Martin O. Iminosugars: from synthesis to therapeutic applications. The atrium southern gate. John Wiley and Sons Ltd, England; 2007
112. von Itzstein M, Wu WY, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993;363:418-423
113. Lew W, Chen X, Kim CU. Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor. Curr Med Chem 2000;7:663-672
114. Rosner H. Use of drug miglitol (Glyset) for treatment of obesity to prevent weight gain for losing weight and for weight control. US6683098; 2004
115. Weinreb NJ, Barranger JA, Charrow J, et al. Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol 2005;80:223-229
116. Zavesca(R) (miglustat) Receives EU Approval For The Treatment of Progressive Neurological Manifestations In Patients With Niemann-Pick Type C Disease. Available from: http://www.medicalnewstoday.com/ articles/137293.php
117. Patterson MC, Vecchio D, Prady H, et al. Miglustat for treatment of Niemann-Pick disease: a randomised controlled study. Lancet Neurol 2007;6:765-772
118. Norez C, Antigny F, Noel S, et al. A cystic fibrosis respiratory epithelial cell chronically treated by miglustat acquires a non-cystic fibrosis-like phenotype. Am J Respir Cell Mol Biol 2009;41:217-225
119. Sun JY, Yang H, Miao S, et al. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo. Phytomedicine 2009;16:1070-1074
120. Sun JY, Zhu MZ, Wang SW, et al. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine. Phytomedicine 2007;14:353-359
121. Chang HH, Asano N, Ishii S, et al. Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients. FEBS J 2006;273:4082-4092
122. Fan JQ, Ishii S. Active-site-specific chaperone therapy for Fabry disease. Yin and Yang of enzyme inhibitors. FEBS J 2007;274:4962-4971
123. Fun J-Q. Iminosugars as active-site-specific chaperones fort he treatment of lysosomial storage disorders. In: Compain P, editor, Iminosugars, from synthesis to therapeutic applications. Wiley, Martin OR; 2007
124. Mowery P, Yang Z-Q, Gordon EJ, et al. Synthetic glycoprotein mimics inhibit L-selectin-mediated rolling and promote L-selectin shedding. Chem Biol 2004;11:725-732
125. Cipolla L, Airoldi C, Galliani P, et al. LPS biogenetic pathway: enzyme characterisation and synthetic efforts towards inhibitors. Curr Org Chem 2008;12:576-600
126. Simanek EE, McGarvey GJ, Jablonowski JA, Wong CH. Selectin-carbohydrate interactions: from natural ligands to designed mimics. Chem Rev 1998;98:833-862
127. Zollner TM, Asadullah K. Selectin and selectin ligand binding: a bittersweet attraction. J Clin Invest 2003;112:980-983
128. Lynn M, Rossignol DP, Wheeler JL, et al. Blocking of responses to endotoxin by E5564 in healthy volunteers with experimental endotoxemia. J Infect Dis 2003;187:631-639
129. Piazza M, Rossini C, Della Fiorentina S, et al. Glycolipids and Benzylammonium lipids as novel antisepsis agents: synthesis and biological characterization. J Med Chem 2009;52:1209-1213
130. Christ WJ, Rossignol DP, Kobayashi S, Kawata T. Substituted liposaccharides useful in the treatment and prevension of endotoxemia. US5935938; 1999
131. Shipp EL, Hsieh-Wilson LC. Profiling the sulfation specificities of glycosaminoglycan interactions with growth factors and chemotactic proteins using microarrays. Chem Biol 2007;14:195-208
132. Raman R, Sasisekharan V, Sasisekharan R. Structural insights into biological roles of protein-glycosaminoglycans interactions. Chem Biol 2005;12:267-277
133. Spassova MK, Bornmann WJ, Ragupathi G, et al. Synthesis of selected LeY and KH-1 analogues: a medicinal chemistry approach to vaccine optimization. J Org Chem 2005;70:3383-3395
134. Krug LM, Ragupathi G, Hood C, et al. Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin Cancer Res 2004;10:6094-6100 (Pubitemid 39287514)
135. Chefalo P, Pan Y, Nagy N, et al. Preparation and immunological studies of protein conjugates of N-acylneuraminic acids. Glycoconj J 2004;20:407-414
136. Marcaurelle LA, Pratt MR, Bertozzi CR. Synthesis of thioether-linked analogues of the 2,3-Sialyl-TF and MECA-79 antigens: mucin-type glycopeptides associated with cancer and inflammation. ChemBioChem 2003;2-3:224-228
137. Pan Y, Chefalo P, Nagy N, et al. Synthesis and immunological properties of N-modified GM3 antigens as therapeutic cancer vaccines. J Med Chem 2005;48:875-883
138. Hanessian S. Total synthesis of natural products: the "Chiron" approach. Pergamon: Oxford; 1983
139. Hollingsworth RI, Wang G. Toward a carbohydrate-based chemistry: progress in the development of general-purpose chiral synthons from carbohydrates. Chem Rev 2000;100:4267
140. Hirschmann RF, Nicolaou KC, Angeles AR, et al. The beta-D-Glucose scaffold as a gamma-turn mimetic. Acc Chem Res 2009;42:1511-1520
141. Velter I, La Ferla B, Nicotra F. Carbohydrate based molecular scaffolding. J Carb Chem 2006;25:97-138
142. Cipolla L, Peri F, La Ferla B, et al. Glycidic scaffolds for the production of bioactive compounds. Curr Org Synth 2005;2:153-173
143. Meutermans W, Le GT, Becker B. Carbohydrates as scaffolds in drug discovery. Chem Med Chem 2006;1:1164-1194
144. Le GT, Abbenante G, Becker B, et al. Molecular diversity through sugar scaffolds. Drug Discov Today 2003;8:701-709
145. Capozzi G, Giannini S, Menichetti S, et al. Design, synthesis and biological activity of carbohydrate containing peptidomimeticis as new ligands for the human Tachykinin NK-2 receptor. Bioorg Med Chem Lett 2002;12:2263-2266
146. Peri F, Bassetti R, Caneva E, et al. Arabinose-derived bicyclic amino acids: synthesis, conformational analysis and construction of an alphavbeta3-selective RGD peptide. J Chem Soc Perkin Trans I 2002;5:638-644
147. Hungerford NL, Fleet GWJ. Tetrahydrofuran amino acids: beta and gamma-azidotetrahydrofurancarboxylic acid monomers derived from D-glucoheptonolactone as building blocks for beta and gamma oligopeptides. J Chem Soc Perkin Trans I 2000:3680-3685
148. Chrétien F, Moitessiera N, Roussela F, et al. Carbohydrate-based mimics of D-myo-Inositol 1,4,5-Trisphosphate. Curr Org Synth 2000;4:513-534
149. Cipolla L, Redaelli C, Granucci F, et al. Straightforward synthesis of novel Akt inhibitors based on a glucose scaffold. Carbohydr Res 2010; DOI: 10.1016/j.carres.2009.12.013
150. Cervi G, Peri F, Battistini C, et al. Bicyclic carbohydrate-derived scaffolds for combinatorial libraries. Bioorg Med Chem 2006;14:3349-3367
151. Cipolla L, Forni E, Jiménez-Barbero J, Nicotra F. Synthesis and conformational analysis of fructose-derived scaffolds: molecular diversity from a single molecule. Chem Eur J 2002;8:3976-3983
152. Palmioli A, Sacco E, Airoldi C, et al. Selective cytotoxicity of a bicyclic Ras inhibitor in cancer cells expressing K-RasG13D. Biochem Biophys Res Commun 2009;386:593-597
153. Zhang H, Ma Y, Sun X-L. Recent developments in carbohydrate-decorated targeted drug/gene delivery. Med Res Rev 2010;30:270-289
154. Araújo AC, Nicotra F, Costa B, et al. Fructose-fused gamma-butyrolactones and lactams - synthesis and biological evaluation as GABA receptor ligands. Carbohydr Res 2008;343:1840-1848
155. Araújo AC, Nicotra F, Airoldi C, et al. Synthesis and biological evaluation of novel rigid 1,4-benzodiazepine-2,5-dione chimeric scaffolds. Eur J Org Chem 2008:635-639